Graphene oxide quantum dots-loaded sinomenine hydrochloride nanocomplexes for effective treatment of rheumatoid arthritis via inducing macrophage repolarization and arresting abnormal proliferation of fibroblast-like synoviocytes.

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.

Sex-related differences in safety profiles, pharmacokinetics and tissue distribution of sinomenine hydrochloride in rats.

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum (Thunb.) Rehd. et Wils which exhibits significant analgesic, anti-inflammatory, and immunosuppressive effects. Sinomenine hydrochloride (SH) preparations, classified as natural disease-modifying antirheumatic drugs, are currently available for the treatment of rheumatoid arthritis and other rheumatic diseases. Our toxicity evaluation demonstrated that the median lethal dose of SH in female Sprague-Dawley (SD) rats was over 11 times greater than that in male SD rats, revealing striking sex-linked differences in the safety profile of SH. The present study was designed to investigate differences in the pharmacokinetics (PKs) and tissue distribution of SH between male and female SD rats after a single oral dose of 25 mg/kg. PK and tissue distribution studies were performed using a validated UPLC-MS/MS method. The results showed that SH-treated SD female rats displayed markedly greater drug exposure, and SH exhibited a longer half-life and slower clearance rate than comparable studies in male rats. Moreover, the tissue distribution study confirmed that the sinomenine concentration in female rats was considerably greater in the internal organs than in male rats. Our study demonstrates, for the first time, significant sex-related differences in the safety profile and PKs of SH, which may be associated with a distinct sex-dependent metabolic mechanism of sinomenine.

Multifunctional nanoparticles of sinomenine hydrochloride for treat-to-target therapy of rheumatoid arthritis via modulation of proinflammatory cytokines.

Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant of Sinomenium acutum (Thunb.) Rehd.et Wils. Currently, sinomenine hydrochloride (SIN) preparations, classified as a natural disease-modifying anti-rheumatic drug (nDMARD), have been used for therapy of rheumatoid arthritis (RA); however, the efficacy of SIN was seriously limited by its short half-life, low bioavailability, and dose-dependent adverse reactions. In this study, a biomimetic nanocomplex based on Prussian blue nanoparticles (PB NPs) was developed for overcoming clinical limitations of SIN and accordingly improving its efficacy. In vitro studies showed that the nanocomplexes significantly inhibited abnormal proliferation of fibroblast-like synoviocytes (FLSs) by scavenging reactive oxygen species (ROS) and inhibiting secretion of proinflammatory cytokines. In vivo imaging demonstrated that the improved immune-escape properties of the nanocomplexes resulted in markedly increased half-life of circulation and levels of accumulated drugs at arthritic sites of adjuvant-induced arthritis (AIA) rats. Notably, the nanocomplexes significantly suppressed joint inflammation and protected against bone destruction of AIA rats by inhibiting inflammatory cytokine secretion of the synovial macrophages and FLSs. These results indicate that the nanocomplexes provide an excellent carrier for controlled release and targeted accumulation of SIN within the arthritic sites, which consequently achieve disease-remitting effects of SIN on RA.

Lactate metabolism in rheumatoid arthritis: Pathogenic mechanisms and therapeutic intervention with natural compounds.

BACKGROUND: Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease characterized by persistent inflammation and hyperplasia of the synovial membrane, the degradation of cartilage, and the erosion of bones in diarthrodial joints. The inflamed joints of patients with RA have been recognized to be a site of hypoxic microenvironment which results in an imbalance of lactate metabolism and the accumulation of lactate. Lactate is no longer considered solely a metabolic waste product of glycolysis, but also a combustion aid in the progression of RA from the early stages of inflammation to the late stages of bone destruction. PURPOSE: To review the pathogenic mechanisms of lactate metabolism in RA and investigate the potential of natural compounds for treating RA linked to the regulation of imbalance in lactate metabolism. METHODS: Research advances in our understanding of lactate metabolism in the pathogenesis of RA and novel pharmacological approaches of natural compounds by targeting lactate metabolic signaling were comprehensively reviewed and deeply discussed. RESULTS: Lactate produced by RA synovial fibroblasts (RASFs) acts on targeted cells such as T cells, macrophages, dendritic cells and osteoclasts, and affects their differentiation, activation and function to accelerate the development of RA. Many natural compounds show therapeutic potential for RA by regulating glycolytic rate-limiting enzymes to limit lactate production, and affecting monocarboxylate transporter and acetyl-CoA carboxylase to inhibit lactate transport and conversion. CONCLUSION: Regulation of imbalance in lactate metabolism offers novel therapeutic approaches for RA, and natural compounds capable of targeting lactate metabolic signaling constitute potential candidates for development of drugs RA.

A pH-Driven indomethacin-loaded nanomedicine for effective rheumatoid arthritis therapy by combining with photothermal therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by inflammatory micro-environments in the joints. Indomethacin (IND), a conventional nonsteroidal anti-inflammatory drug (NSAID), has been used for the therapy of RA. However, the poor solubility and serious side effects of oral administration of IND significantly limit its efficacy. In this study, we have synthesized biomimetic IND-loaded Prussian blue (PB) nanoparticles (IND@PB@M@HA) with hyaluronic acid (HA) modification for increasing the solubility and targeting the ability of IND to the inflamed joints. The application of hybrid cell membranes on the NPs endowed immune escape of IND@PB@M@HA NPs, which accordingly extended the circulation time in the blood. In vitro assay demonstrated that the combination of nanomedicine and photothermal therapy produced a powerful anti-inflammatory effect by reducing the levels of inflammatory factors and cell viability of activated macrophages and NPs possessed obvious pH-responsiveness. In vivo assay demonstrated that the nanomedicine for synergistic photothermal therapy exhibited desirable pharmacodynamics and pharmacokinetic properties at ultra-low drug dosage in a rat model of adjuvant-induced arthritis, which was confirmed by inflammatory suppression, bone erosion remission, and negligible adverse effects. In summary, the proposed nanomedicine has the potential role for targeted anti-inflammatory therapy of RA.

Clinical application of new self-designed implanting applicator in vaginal three-dimensional intracavitary brachytheraypy after hysterectomy for gynecological cancer / 中华放射肿瘤学杂志

Objective:Investigate the safety and feasibility of using the new self-designed implanting applicator in vaginal three-dimensional intracavitary brachytherapy after hysterectomy for gynecological cancer, and to explore the clinical value of the self-designed implanting applicator.Methods:Sixty-two gynecological cancer patients who underwent brachytherapy in Sun Yat-sen University Cancer Center were selected in this study. Each patient received three-dimensional intracavitary brachytherapy because of the indication of postoperative radiotherapy. Each patient was treated with different types of self-designed implanting applicators according the condition of postoperative vagina,and the vaginal tube and implant needle were placed in the template according to the preset channnel. Based on the actual CT images, the high-risk clinical target volume (HR-CTV), and organs at risk were defined according to unified target area delineation criteria and then the brachytherapy plan was conducted. The prescription dose of high-risk clinical target volume (HR-CTV) was 5.5 Gy/time. The parameters such as target area, organs at risk volume and irradiated dose were evaluated by DVH diagram.Results:Sixty-two patients successfully completed brachytherapy under the guidance of self-designed implanting applicator. A total of 140 implantation treatments were performed. The total average dose of HR-CTV D90% was (575.48±22.30) cGy, the mean dose D 2cm3 of bladder, rectum and sigmoid colon were (328.69±102.71), (369.14±46.59) and (27.28±71.27) cGy, the small intestine did not drop the target area, so there was no statistics. There was statistical significance between target volume and organs at risk dose ( P<0.05). Conclusions:The new self-designed implanting applicator has obvious clinical advantages in vaginal three-dimensional intracavitary brachytherapy after hysterectomy for gynecological cancer, meets the requirements of the preset planning dose,and it is sample to operate and highly safe,which indicated a bright future of the clinical application.

Explore Effective Constituents and Mechanism of Tingli Dazao Xiefeitang in Treatment of Heart Failure Based on Network Pharmacology and Mass Spectrometry / 中国实验方剂学杂志

Objective:To investigate the effective constituents and mechanism of Tingli Dazao Xiefeitang for the treatment of heart failure through network pharmacology and high resolution mass spectrometry technique as well as molecular docking technique. Method:Chemical components and potential targets in Descurainiae Semen Lepidii Semen and Jujubae Fructus were searched by referring to literature and BATMAN-TCM database. The disease targets were searched in GeneCards database with ''heart failure'' as the key word. STRING platform was used to construct protein-protein interaction（PPI） network based on common targets of drugs and disease. The network topology was analyzed by using Cytoscape 3.7.2 software to obtain the core targets eventually. Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis of the core targets was conducted through DAVID database to draw a network of “herb-compound-target-pathway”. Based on the results of the network pharmacology research above，high resolution mass spectrometry was used to analyze the decoction and confirm the selected active components. AutoDock 4.2.6 software was used for molecular docking verification of key active components and related targets. Result:A total of 85 components were obtained in Descurainiae Semen Lepidii Semen，and 49 components were obtained in Fructus Ziziphi Jujubae. A total of 1 078 drug targets and 1 549 disease targets were identified. After PPI analysis and network topology analysis，23 core targets and 33 active components were obtained，involving 19 signaling pathways （<italic>P</italic><0.05）. Mass spectrometry analysis results indicated that 18 components such as isovanillic acid，descuraininA and kaempferol-7-<italic>O-β-D</italic>-glucopyranoside were confirmed in decoction. Molecular docking analysis results indicated that 6 core components （degree value top 6），such as isovanillic acid，descurainin A and kaempferol-7-<italic>O-β-D</italic>-glucopyranoside，had good binding activity with silent information regulatory factor 1（SIRT1），interleukin（IL）1B，protein kinase B<italic>α</italic>（AKT1） and tumor necrosis factor（TNF）. The compound recipe for heart failure mainly involved mitogen-activated protein kinase（MAPK），hypoxia inducible factor-1（HIF-1），Mammalian target of rapamycin（mTOR） and other signaling pathways. Conclusion:This study preliminarily investigated the effective constituents and mechanism of Tingli Dazao Xiefeitang in the treatment of heart failure. It can provide references for the precise clinical medication and screening of quality control markers，as well as the discovery of active components in the treatment of heart failure.

The clinical application of magnetic resonance-guided radiotherapy / 中华放射肿瘤学杂志

Objective:To investigate the clinical feasibility of the Unity radiotherapy system guided by magnetic resonance imaging.Methods:Twenty-four patients were enrolled and received a total of 384 fractions of treatment at Unity system. According to the treatment site, all patients were divided into head-neck, abdomen-thorax, pelvic, spine and limb groups. The patients were set-up without external laser. And then, the time required at different stages in online treatment process and the registration error of each fraction were separately calculated. The geometric deformations of MR images were weekly measured by using MR geometric deformation phantom. At last, the Arccheck was used to perform the dose verification of reference plan, online plan and offline plan.Results:The mean duration of radiotherapy in the five groups were 29.1, 27.6, 26.6, 25.6 and 32.0 min, respectively. The set-up errors in the left-right, superior-inferior and anterior-posterior direction in the five groups were: head-neck group (0.08±0.06 cm, 0.16±0.13 cm, 0.08±0.05 cm), abdomen-thorax group (0.23±0.18 cm, 0.50±0.47 cm, 0.12±0.1 cm), pelvic group (0.25±0.19 cm, 0.32±0.25 cm, 0.11±0.09 cm), spine group (0.46±0.38 cm, 0.26±0.26 cm, 0.13±0.07 cm) and limb group (0.33±0.30 cm, 0.34±0.23 cm, 0.08±0.06 cm), respectively. In the central region, the geometric deformation of MR was less than 0.3 mm, and that of the sphere with a diameter of 500 mm was less than 2.1 mm. The meanγ pass rate of the reference plan, online plan and offline plan were 97.92%, 97.84% and 94.58%, respectively.Conclusions:MR-guided radiotherapy has great potential for clinical application, whereas the process of Unity system is relatively complex. The synergy of different departments has a great impact on the treatment, which needs further optimization.

Virologic and clinical characteristics for prognosis of severe COVID-19: a retrospective observational study in Wuhan, China

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. MethodsA total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. ResultsA total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. ConclusionsPatients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

Current advance in the application of anti-vascular endothelial growth factor drugs in wet age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

@#Age-related macular degeneration(ARMD)is one of the main causes which lead to irreversible blindness. Wet ARMD, which is featured by choroidal neovascularization(CNV), takes up 90% in ARMD related blind patients. With the increasing population of aged people in China, wet ARMD has become a severe social and medical issues. Currently, management aiming at wet ARMD is the applications of anti-VEGF agents. Anti-VEGF drugs not only postpone the development of CNV, but also preserve the visual function, improve the prognosis, and reduce the incidence of blindness. However, we still need to focus on the non-response during treatment, long-term maintenance, drug resistance, adverse reactions, and economic effectiveness. Here we review the recent clinical medications on wet ARMD.

Gait Characteristics of Staircase Walking of Old and Young Adults under Dual Task Situation / 中国康复理论与实践

Objective:To compare the biomechanical characteristics and cognitive task performance of the young and the old adults as ascending and descending staircase. Methods:From March to April, 2018, 25 volunteers, including twelve old persons aged (71.54±3.25) and 13 young persons aged (22.24±1.56), were tested with continuous minus seven as sitting (pre-test), walking up and down stairs, walking up and down stairs with continuous minus seven and continuous minus seven as sitting again (post-test). Results:The performance of continuous minus seven was better as walking up stairs and post-test than pre-test in the old persons, and it was better as both up and down stairs, as well as post-test than pre-test in the young persons. As walking up stairs, the main effects of both age (F > 5.037,P < 0.05) and task (F > 6.122,P < 0.05) were significant in walking time, step length, frequency and speed; while walking down stairs, the main effects of both age (F > 17.252,P < 0.01) and task (F > 6.274,P < 0.05) were significant in walking time, step frequency and speed. Conclusion:People would alter the focus on cognitive tasks according to the difficulty of the action. The old adults would be more conservative in the action as upstair during the dual task, and would pay less attention to cognitive task additionally as downstair.

Dosimetric comparison between CT-guided free-hand intracavity/interstitial adaptive brachytherapy and conventional point-A brachytherapy in the treatment of cervical cancer / 中华放射肿瘤学杂志

Objective:To analyze the dosimetric differences between CT-guided free-hand intracavity/interstitial brachytherapy[image-guided adaptive brachytherapy (IGABT)] and conventional point-A plan (CP) in the treatment of cervical cancer.Methods:Twenty-six cervical cancer patients who received four cycles of IGABT in Sun Yat-sen University Cancer Center were enrolled in this study. Two sets of CT images were obtained before and after applicator adjustment to aid in the design of CP and IGABT plans. The high-risk clinical target volume (HRCTV), point A, and organs at risk (bladder, rectum, and sigmoid colon) were defined on CT images. CP and IGABT plans were designed on CT images. Parameter differences between CP and IGABT plans were analyzed with paired t-test and Wilcoxon test. Results:According to the coverage index (CI) of CP, plans were divided into two groups: in group A (CI≥0.90), 20 CP and corresponding IGABT plans were included, and 84 CP and corresponding IGABT plans in group B (CI<0.90). The mean volume of HRCTV and mean tumor diameter in group A were significantly smaller than those in group B (46.7 cm 3vs. 62.1 cm 3, P<0.001 and 3.1 cm vs. 4.4 cm, P<0.001). Compared with CP, IGABT significantly improved the value of D 90% in all plans and group B, whereas lowered the bladder dose. IGABT also reduced the dose of sigmoid colon in group A. IGABT significantly improved conformal index and dose homogeneity index. Conclusions:IGABT can significantly improve the target coverage, conformal index and dose homogeneity index, protect organs at risk. Compared with CP, IGABT has advantages in the treatment of patients with bulky tumor.

Factors predicting 2014 ISUP pathology grade upgrading from prostate biopsy to radical prostatectomy pathology / 中华泌尿外科杂志

Objective To investigate the risk factors predicting pathology grade upgrading after radical prostatectomy using the 2014 International Society of Urologic Pathology (ISUP) grading system.Methods A total of 205 patients who underwent biopsy and radical prostatectomy from January 2017 to December 2018 were reviewed retrospectively.The median and range of the patients' age,PSA level,prostate volume,number of biopsy core examined,Gleason score and ISUP grade were 66 (45-81) years old,17.16(0.89-1254.00)ng/ml,36.4(4.1-152.1) rnl,10(1-15),7(6-10),and 3(1-5) respectively.The patients were divided into group of upgrading ISUP grade and group without upgrading ISUP grade.Multivariate Logistic regression analysis and receiving operating characteristic curve analysis were performed to identify predictors of ISUP upgrading and determine the optimal cut off value respectively.Result The median and range of Gleason score and ISUP grade after radical prostatectomy were 7 (6-10),and 3 (1-5) respectively.The radical prostatectomy ISUP grade upgraded in 73 (35.6％) out of 205 cases when compared with biopsy ISUP grade.Radical prostatectomy ISUP grades were concordant in 91 cases (44.4％) and downgraded in 41 cases(20.0％).Of 101 with biopsy ISUP grades less than or equal to 2,the ISUP grade of radical prostatectomy upgraded in 58 cases (57.4％),while radical prostatectomy ISUP grade upgraded in only 18 (26.9％) of 67 patients with biopsy ISUP grades of 3 or 4.Biopsy ISUP grades represent an independent predictor for ISUP grade upgrading after radical prostatectomy (OR =0.496,P ＜ 0.001).Conclusion Patients with biopsy ISUP grades less than or equal to 2 are at great risk of ISUP grade upgrading after radical prostatectomy.

Expressions of miR-146a and miR-155 in different samples of chronic hepatitis B patients / 中南大学学报(医学版)

To detect the levels of miR-146a and miR-155 in different samples from chronic hepatitis B (CHB), reveal whether there is a correlation between the 2 miRNAs in different samples, and to provide a theoretical basis for sample choice of miRNA research in liver.
 Methods: Real-time PCR was conducted to examine the expression of miR-146a and miR-155 in the plasma, peripheral blood mononuclear cell (PBMC), and liver tissues from 41 CHB patients who underwent nucleoside analogues antiviral therapy for 104 weeks. Correlations between the levels of miR-146a and miR-155 among the 3 samples were analyzed.
 Results: The expressions of miR-146a and miR-155 in the plasma, PBMC and liver tissues were significantly down-regulated at the 104th week than those at the baseline (all P0.05).
 Conclusion: Compared with PBMC, miR-146a and miR-155 from plasma can better reflect the expression in the liver tissues, suggesting that plasma can be applied in the mechanism research on miR-146a and miR-155 in the liver diseases instead of liver tissues.

Expression profiles of the exosomal miRNAs in the chronic hepatitis B patients with persistently normal ALT / 中南大学学报(医学版)

Objective:To investigate expression profiles of the plasma exosomal miRNAs of the chronic hepatitis B (CHB) patients with persistently normal alamine aminotransferase (PNALT) for the first time and try to find exosomal miRNAs which could reflect liver inflammation better.Methods:Five CHB patients with liver tissue inflammation grade ≥A2 of PNALT and 5 CHB patients with liver tissue inflammation grade ＜A2 of PNALT were enrolled and their blood samples were collected.The exosomes were extracted from these blood samples and measured by electron microscope to determine the extraction effect.The exosomal miRNAs were extracted and sent for high throughput sequencing,and the expression of exosomal miRNAs in the 2 groups of patients was analyzed.Results:Under the electron microscope,exosomes were small membranous vesicles with 30-100 nm in diameter.The peak value of particle size ranged from 10 to 100 nm.High throughput sequencing showed that there were 591 differentially expressed exosomal miRNAs between the 2 groups.Compared with the control group,18 exosomal miRNAs were up-regulated and 6 exosomal miRNAs were down-regulated in PNALT patients with the liver tissue inflammation grade ≥ A2.Conclusion:Exosomal miRNAs in the CHB patients with PNALT who have the different grades of liver inflammation are differently expressed.Some of the differently expressed exosomal miRNAs are expected to be sensitive biomarkers for timely assessment of liver inflammation in the CHB patients with PNALT.

Progress in three-dimensional MRI-guided brachytherapy for cervical cancer / 中华放射肿瘤学杂志

Cervical cancer is one of the leading causes of death in women with malignancies worldwide.Brachytherapy plays an essential role in the radiation therapy for cervical cancer, and its combination with external beam radiation is indicated for previously untreated or recurrent cervical cancer at various stages without distant metastasis.Magnetic resonance imaging (MRI) has superior resolution of soft tissue, which allows for accurate delineation of target volume, protects organs at risk (OARs), and thus improves treatment outcomes.In recent years, many studies have demonstrated the feasibility and superiority of three-dimensional MRI-guided brachytherapy for cervical cancer.This article aims to elaborate on relevant MRI techniques, selection of applicators, delineation of target volume and OARs, evaluation of treatment plans, and the clinical effect of three-dimensional MRI-guided brachytherapy.

Combination of Internal-braceTM technology and modified Brostrom procedure for treatment of chronic ankle instability / 中华创伤杂志

Objective To investigate the surgical methods and short-term effects of Internal-braceTM technology combined with modified Brostrom procedure for treatment of chronic ankle instability.Methods A retrospective case series study was made on 17 patients with chronic ankle instability treated using the Internal-braceTM technology combined with modified Brostrom procedure from May 2015 to April 2016.There were 10 males and 7 females,at age of 24 and 36 years (mean,31.8 years).A left ankle injury occurred in 6 patients and a right ankle injury in 11 patients.Operation time,postoperative complications and incision healing was documented after operation.Ankle stability was tested using the anterior drawer test and lateral stress test,and ankle range of motion was detected.American orthopedic foot and ankle society (AOFAS) score was used for postoperative efficacy evaluation.Results Operation time was 45 to 84 minutes (mean,64.5 minutes).None of the patients revealed neurological deficits after operation.All incisions healed by the first intension.Full weight bearing was started two weeks after operation.All patients were followed up for mean 3.5 months (range,1-6 months).At the final follow-up,both anterior drawer test and lateral stress test were negative.All patients had a normal range of motion of the ankle after operation.AOFAS score was increased from preoperative (36.2 ± 13.4)points to (91.2 ± 6.7) points at the final follow-up (P ＜ 0.01).According to the AOFAS score,the results were excellent in 15 patients and good in 2 patients,with the good rate of 100％.Conclusion For chronic ankle instability,Internal-braceTM technology comnbined with modified Brostrom procedure benefits wound healing and functional recovery,reduces incidence of complications and exhibits satisfactory short-term outcome.

Clinical effect of interventional embolization for patients with ruptured anterior communicating artery aneurysm and their cognitive function / 局解手术学杂志

Objective To investigate the effect of interventional embolization on the clinical outcome and cognitive function of patients with anterior communicating artery aneurysm rupture .Methods The data of 120 patients with anterior communicating artery aneurysm rup-ture in our hospital from January 2016 to January 2017 were retrospectively analyzed ,in which 71 cases were treated by the spring coil emboli-zation,21 cases received balloon-assisted coiling,23 cases received stent-assisted coil embolization .At the same time,50 healthy people were collected as control group .The preoperative , postoperative cognitive function and the clinical effect of the patients were evaluated .Results Coil embolization group completed embolism in 29 cases,40 cases of most embolism ,2 cases of partial embolization;balloon-assisted coiling group completed embolism in 16 cases,4 cases of most embolism ,1 cases of partial embolization;17 cases of stent assisted coil embolization group completed embolism ,3 cases of most embolism ,3 cases of partial embolism .There was statistically significant difference in embolization rate of coil embolization group(χ2 =6.8862,P=0.0320),balloon-assisted coiling group(χ2 =15.900,P=0.0004) and stent assisted coil embolization group(χ2 =7.280,P=0.0262).After the treatment,the difference in cognitive function of coil embolization group (24.0 ± 0.2) and balloon-assisted coiling group(24.3 ±0.2) was statistically significant (t=86.0386,P=0.0000);the difference between coil embolization group(24.0 ±0.2) and balloon-assisted coiling group(24.3 ±0.2) was statistically significant(t=46.3848,P=0.0000);the difference between balloon-assisted coiling group(24.3 ±0.2) and stent assisted coil embolization group (21.5 ±0.2) points was statisti-cally significant(t=52.1002,P=0.0000).Conclusion Different interventional embolization techniques can improve the cognitive func-tion of patients with ruptured anterior communicating artery aneurysm ,which has more obviously effect on the cognitive function of patients with stent assisted coil embolization .

Elevated TRAF4 expression impaired LPS-induced autophagy in mesenchymal stem cells from ankylosing spondylitis patients

Ankylosing spondylitis (AS) is a type of autoimmune disease that predominantly affects the spine and sacroiliac joints. However, the pathogenesis of AS remains unclear. Some evidence indicates that infection with bacteria, especially Gram-negative bacteria, may have an important role in the onset and progression of AS. Recently, many studies have demonstrated that mesenchymal stem cells (MSCs) dysfunction may contribute to the pathogenesis of many rheumatic diseases. We previously demonstrated that MSCs from AS patients exhibited markedly enhanced osteogenic differentiation capacity in vitro under non-inflammatory conditions. However, the properties of MSCs from AS patients in an inflammatory environment have never been explored. Lipopolysaccharide (LPS), a proinflammatory substance derived from the outer membrane of Gram-negative bacteria, can alter the status and function of MSCs. However, whether MSCs from AS patients exhibit abnormal responses to LPS stimulation has not been reported. Autophagy is a lysosome-mediated catabolic process that participates in many physiological and pathological processes. The link between autophagy and AS remains largely unknown. The level of autophagy in ASMSCs after LPS stimulation remains to be addressed. In this study, we demonstrated that although the basal level of autophagy did not differ between MSCs from healthy donors (HDMSCs) and ASMSCs, LPS-induced autophagy was weaker in ASMSCs than in HDMSCs. Specifically, increased TRAF4 expression in ASMSCs impaired LPS-induced autophagy, potentially by inhibiting the phosphorylation of Beclin-1. These data may provide further insight into ASMSC dysfunction and the precise mechanism underlying the pathogenesis of AS.

Effect of microRNA on proliferation caused by mutant HBx in human hepatocytes / 中华肝脏病杂志

To study the effect of micro (mi)RNA on cellular proliferation induced by hepatitis B x protein, HBx, in human liver cells and to investigate the underlying molecular mechanism of this cancer-related effect. The human L02 hepatocyte cell line was stably transfected with HBx (L02/HBx) or an HBx mutant (L02/HBx-d382) that induces higher levels of cellular proliferation. The differential miRNA expression profiles were determined by microarray analysis and confirmed by real-time PCR. Two miRNAs, miR-338-3p and miR-551b, that were found to be significantly down-regulated in the L02/HBx-d382 cells were selected for further study and transfected individually into cells using the lipofectamine procedure. The cell survival rate was analyzed by MTT assay, and cell cycles were assessed by flow cytometry. Expressions of cyclinD1, cyclinG1, and E2F1 were assessed by real-time PCR and Western blotting. Compared with the microarray miRNA profile of L02/pcDNA3.0 cells, six miRNAs were up-regulated and five miRNAs were down-regulated in the L02/HBx-d382 cells, while four miRNAs were up-regulated and 12 were down-regulated in the L02/HBx cells. The microarray results were consistent with real-time PCR results. Transfection of miR-338-3p and miR-551b significantly inhibited the cell survival rates (P less than 0.001) and induced G0/G1 phase cycle arrest. According to MTT results: for L02/HBx-d382 cells, compared with lipofectamine or non-transfected (NC) controls, the t value of miR-338-3p was 10.402, 9.133 and the t value of miR-551b was 8.763, 7.403; for L02/HBx cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 9.105, 8.074 and the t value of miR-551b was 7.673, 7.52. According to flow cytometry results: for L02/HBx-d382 cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 12.173, 11.107 and the t value of miR-551b was 15.364, 13.377; for L02/HBx cells, compared with lipofectamine or NC controls, the t value of miR-338-3p was 15.416, 13.378, and the t value of miR-551b was 13.276, 13.109. The protein levels of cyclinD1, cyclinG1, and E2F1 were significantly reduced by both miR-338-3p and miR-551b ( P less than 0.001). For L02/HBx-d382 cells, compared with lipofectamine or NC controls: E2F1 had t = 11.132, 10.031 and 12.017, 10.973, respectively; cyclinD1 had t = 15.654, 15.013 and 15.447, 14.733, respectively; cyclinG1 had t = 8.017, 7.661 and 7.402, 7.417, respectively. For L02/HBx cells, compared with lipofectamine or NC controls: E2F1 had t = 14.244, 13.331 and 15.022, 14.468, respectively; cyclinD1 had t = 8.695, 8.137 and 7.877, 7.503, respectively; cyclinG1 had t = 7.73, 7.471 and 7.596, 7.41, respectively. In contrast, the mRNA levels for E2F1, cyclinD1, and cylcinG1 showed no significant differences between the miRNA transfected cells and controls. Wild-type HBx and the high proliferation-inducing mutant HBx can influence the miRNA expression profile of L02 cells. HBx down-regulates miR-338-3p and miR-551b in L02 cells, and the high proliferation-inducing mutant has a more robust effect. The mechanism of miR-338-3p- or miR-551b-mediated cell growth inhibition appears to be related to the direct modulation of cyclinD1, cyclinG1, and E2F1.